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PMID: 17989694 Published · ppublish English Journal Article

Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase.

The EMBO journal ·Vol. 26 ·No. 23 ·2007-11-28 ·Pages 4913-25

De la Peña M, Kyrieleis OJ, Cusack S

Abstract

The vaccinia virus mRNA capping enzyme is a multifunctional heterodimeric protein associated with the viral polymerase that both catalyses the three steps of mRNA capping and regulates gene transcription. The structure of a subcomplex comprising the C-terminal N7-methyl-transferase (MT) domain of the large D1 subunit, the stimulatory D12 subunit and bound S-adenosyl-homocysteine (AdoHcy) has been determined at 2.7 A resolution and reveals several novel features of the poxvirus capping enzyme. The structure shows for the first time the critical role played by the proteolytically sensitive N-terminus of the MT domain in binding the methyl donor and in catalysis. In addition, the poxvirus enzyme has a completely unique mode of binding of the adenosine moiety of AdoHcy, a feature that could be exploited for design of specific anti-poxviral compounds. The structure of the poxvirus-specific D12 subunit suggests that it was originally an RNA cap 2'O-MT that has evolved to a catalytically inactive form that has been retained for D1 stabilisation and MT activity enhancement through an allosteric mechanism.

MeSH Terms
Allosteric Site Amino Acid Sequence Catalytic Domain Crystallography, X-Ray Methyltransferases/chemistry,physiology Models, Molecular Molecular Conformation Molecular Sequence Data Protein Conformation Protein Structure, Tertiary RNA Caps S-Adenosylhomocysteine/chemistry Vaccinia virus/enzymology,genetics
Chemicals
RNA Caps S-Adenosylhomocysteine Methyltransferases mRNA (guanine(N7))-methyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
De la Peña Marcos
Grenoble Outstation, European Molecular Biology Laboratory, Grenoble, France.
Kyrieleis Otto J P
Cusack Stephen
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/sj.emboj.7601912
Published
2007-11-28
Epub
2007-00-08
Pages
4913-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2099473
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601912 PMC Full Text View journal details
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